Objectif Regenerating tissues by reprogramming cells has the potential to become a therapeutic approach for replacing lost tissues in patients suffering from injury or degenerative diseases such as Alzheimer’s or Muscular Dystrophy. Strategies to generate required tissues using embryonic stem cells or induced pluripotent stem cells (iPSCs) are associated with either ethical or medical safety issues. An alternative strategy is to directly reprogram cells to the required tissue type by forced expression of cell fate-inducing transcription factors (TFs). Direct reprogramming (DR) has the potential to circumvent unsafe proliferative pluripotent cell stages and it allows in vivo procedures. However to date, DR is successful in only a few cell types and it is not well understood why most cells are refractory to DR. Recently, we provided evidence that inhibitory mechanisms play an important role in restricting cell fate conversion. We identified factors inhibiting direct conversion of germ cells into specific neurons or muscle cells. Additionally, preliminary studies in our group revealed other factors that inhibit ectopic cell fate induction in somatic cells. The objective of this proposal is to further understand mechanisms that restrict DR. We aim to identify and characterize factors involved in safeguarding differentiated cells and thereby counteract induction of ectopic fates in different cells. We use C. elegans as an in vivo model and apply large-scale forward and reverse genetic screenings with high-throughput. Next generation sequencing, tissue-specific biochemistry (ChIP-seq, SILAC) and 4D imaging will be used to elucidate the molecular function of identified DR-regulating factors. Finally, we will test the ability to convert cells in aged animals and assess the effects of ageing on the ability to induce ectopic cell fates. Our research has the potential to facilitate the generation of specific tissues from different cellular contexts for future biomedical approaches. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicineneurologymuscular dystrophiesmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-StG-2014 - ERC Starting Grant Appel à propositions ERC-2014-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Contribution nette de l'UE € 1 457 938,00 Adresse ROBERT ROSSLE STRASSE 10 13125 Berlin Allemagne Voir sur la carte Région Berlin Berlin Berlin Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 457 938,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Allemagne Contribution nette de l'UE € 1 457 938,00 Adresse ROBERT ROSSLE STRASSE 10 13125 Berlin Voir sur la carte Région Berlin Berlin Berlin Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 457 938,00
